NMR-based metabonomic analysis of normal rat urine and faeces in response to (±)-venlafaxine treatment

Serrano-Contreras, José Iván; García-Pérez, Isabel; Meléndez-Camargo, María Estela; Zepeda, L. Gerardo

doi:10.1016/j.jpba.2016.01.044

Cited by 14 publications

(8 citation statements)

References 30 publications

(4 reference statements)

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“…These studies contain no predictive or prognostic elements and the literature is becoming confused by the mis-naming of such studies. These recent papers appear to be examples of this phenomenon (Park et al, 2013; Wikoff et al, 2013; Serrano-Contreras et al, 2016). …”

Section: Not Pharmacometabonomics!mentioning

confidence: 93%

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

Everett

2016

Front. Pharmacol.

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Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalized medicine, that is the selection of medicines for subgroups of patients so as to maximize drug efficacy and minimize toxicity, is a key goal of twenty-first century healthcare. Currently, most personalized medicine paradigms rely on clinical judgment based on the patient's history, and on the analysis of the patients' genome to predict drug effects i.e., pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as “the prediction of the outcome (for example, efficacy or toxicity) of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures.” The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments.

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Section: Not Pharmacometabonomics!mentioning

confidence: 93%

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

Everett

2016

Front. Pharmacol.

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“…The resulting spectra were manually phased, baseline corrected, and referenced to the 3-(trimethylsilyl) propionate resonance (methyl groups) at 0.0 ppm. Compounds present in urine samples were identified using one-dimensional and two-dimensional NMR experiments, as well as through comparisons of the obtained data with the NMR data in open access databases and literature reports 50 , 51 . Principal component analysis was performed on the 1 H NMR data set by using the AMIX Statistics package (version 3.9.12; Bruker BioSpin, Rheinstetten, Germany).…”

Section: Methodsmentioning

confidence: 99%

Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine production

Rodrigues

Santos

Medeiros

et al. 2018

Sci Rep

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Acute kidney injury (AKI) and metabolic dysfunction are critical complications in sepsis syndrome; however, their pathophysiological mechanisms remain poorly understood. Therefore, we evaluated whether the pharmacological properties of 6-gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI decreased creatinine clearance and renal antioxidant activity, but enhanced oxidative stress and the renal mRNA levels of tumour necrosis factor-α, interleukin-1β, and transforming growth factor-β. Both phenol compounds repaired kidney function through antioxidant activity related to decreased oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis indicated different metabolic profiles for the sham surgery group, caecal ligation and puncture model alone group, and sepsis groups treated with gingerols. 1H nuclear magnetic resonance analysis detected important increases in urinary creatine, allantoin, and dimethylglycine levels in septic rats. However, dimethylamine and methylsulfonylmethane metabolites were more frequently detected in septic animals treated with 6G or 10G, and were associated with increased survival of septic animals. Gingerols attenuated septic AKI by decreasing renal disturbances, oxidative stress, and inflammatory response through a mechanism possibly correlated with increased production of dimethylamine and methylsulfonylmethane.

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“…The acute toxicity group (group II) was administered a single dose of 350 mg/kg VEN. 21 The third group (group III) was treated with 100 mg/kg/d and the dose was increased by 50 mg/kg every 10 days for 30 days. Francesconi et al documented that patients addicted to VEN may use up to 10 to 15 times the therapeutic doses.…”

Section: Methodsmentioning

confidence: 99%

Toxicological Assessment of Venlafaxine: Acute and Subchronic Toxicity Study in Rats

et al. 2018

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Antidepressants are the most commonly prescribed drugs for psychiatric treatment, and venlafaxine (VEN) is one of the most popular options. Venlafaxine is a nontricyclic dual-acting serotonin-norepinephrine reuptake inhibitor. Although an increased incidence of acute toxicity and addiction has been reported, controlled studies examining its toxic effects on different organs are still lacking. This study investigated the possible toxic effects of VEN on the liver, kidney, and gastric tissues. Three groups of rats were administered saline, a single LD dose (350 mg/kg), or 100 mg/kg VEN daily, followed by increases in the dose of 50 mg/kg every 10 days for 30 days (about 10 times the therapeutic doses). The following parameters of liver and kidney injury were then assayed: alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, prothrombin time, partial thromboplastin time, blood urea nitrogen, and serum creatinine. A histopathological examination was then conducted. Both acute and subchronic administration of VEN produced multiple clinical manifestations in the experimental animals, including seizures, coma, and even death. Moreover, the liver and renal function tests indicated injury in these tissues. Furthermore, the histopathological examination showed signs of organ toxicity after both acute and chronic VEN exposure. This study has shown that VEN has harmful effects on the liver, kidney, and stomach in either a single high dose (LD) or repeated exposure to 10 times the therapeutic doses. As a result, strategies to increase awareness of these effects among physicians and the public are needed because this drug may be addictive.

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NMR-based metabonomic analysis of normal rat urine and faeces in response to (±)-venlafaxine treatment

Cited by 14 publications

References 30 publications

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine

Gingerol suppresses sepsis-induced acute kidney injury by modulating methylsulfonylmethane and dimethylamine production

Toxicological Assessment of Venlafaxine: Acute and Subchronic Toxicity Study in Rats

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